Peptide Folding in Translocon-Like Pores

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• The cellular translocon is a vital nanopore across all life domains, essential for protein secretion and membrane protein insertion.
• Recent structures of the archaean SecY translocon show an hourglass-shaped pore, offering insights into protein translocation mechanisms.
• However, the precise peptide folding pathway within the translocon channel before membrane release remains unclear.

Purpose of the Study:

• To investigate atomic-level peptide folding within hourglass-shaped pore models of the SecY translocon.
• To explore the influence of confinement and hydration on peptide folding dynamics.
• To elucidate the mechanisms underlying translocon gating and lateral peptide partitioning.

Main Methods:

• Utilized molecular dynamics simulations to model peptide folding.
• Employed hourglass-shaped pore models based on SecY translocon structures.
• Systematically varied peptide confinement and pore hydration levels.

Main Results:

• Demonstrated that both pore diameter and channel hydration are critical factors influencing peptide folding efficiency.
• Showed that these factors significantly affect the helical stability of the translocating peptide.
• Provided atomic-level insights into the peptide folding process within the translocon channel.

Conclusions:

• Pore geometry and hydration level are key determinants of translocon function.
• Findings offer crucial insights into the gating mechanisms and lateral partitioning of peptides within the translocon.
• This study advances our understanding of protein translocation and membrane insertion processes.